Many chemokines including CCL20/MIP-3α display antimicrobial activity

Abstract

Previous studies have demonstrated that beta-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3alpha (MIP-3alpha). Structural analysis of CCL20/MIP-3alpha revealed that most of the positively charged residues are concentrated at one area of its topological surface, a characteristic considered to be important for the antimicrobial activity of defensins. Here, we report that similar to defensins, CCL20/MIP-3alpha has antimicrobial effects on Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus, and Candida albicans. Additionally, by screening a total of 30 human chemokines, we have identified an additional 17 human chemokines, which exhibit antimicrobial activity in vitro. Collectively, about two-thirds of the chemokines investigated so far has the capacity to kill microorganisms in vitro, suggesting that antimicrobial activity may be another host-defense function for certain chemokines. Comparison of the structural characteristics between antimicrobial and nonantimicrobial chemokines suggests that topological formation of a large, positively charged electrostatic patch on the surface of the molecule is likely to be a common structural feature of antimicrobial chemokines.

Macrophage inflammatory protein 3α deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus

“…The exact mechanism by which MIP-3α exhibits its anti-viral activity is not known, however the high isoelectric point (pI>10.6) and specific distribution of positively charged residues suggests a direct interaction with the negatively charged viral envelope. 8,9,23 The current study demonstrates that chemokines such as MIP-3α exhibits anti-viral activity against VV and further demonstrates a role for MIP-3α in controlling VV pathogenesis. Additionally, we demonstrate that insufficient expression and production of MIP-3α in AD skin increases the potential for disseminated VV infection following smallpox vaccination.…”

“…9,11,23 Using gene chip microarrays, we previously observed elevated expression of MIP-3α in the lesional inflamed skin of psoriasis patients as compared to inflamed skin lesions from AD patients. 4 We confirmed this observation in the current study using real-time RT-PCR and immunohistochemistry which have a higher degree of sensitivity and reproducibility.…”

“…8 In recent years, chemokines have been shown to exhibit anti-bacterial activity and therefore may serve as a new class of anti-microbial molecules. 9 In particular, macrophage inflammatory protein (MIP-) 3α (CCL20) is a C-C chemokine constitutively expressed by keratinocytes in the epidermis. 10 It is additionally expressed by endothelial cells, monocytes, and fibroblasts following stimulation 11 and neutrophils in response to microbial pathogens.…”

Candida albicans Triggers Activation of Distinct Signaling Pathways to Establish a Proinflammatory Gene Expression Program in Primary Human Endothelial Cells

“…CCL20/MIP-3␣, another previously unknown Candida-regulated endothelial chemokine, belongs to a subgroup of chemokines with defensin-like antimicrobial activity (29) and is a potent chemoattractant for dendritic cell precursors. CCL20/MIP-3␣ thus has the properties to act as a danger signal, thereby linking the innate to the adaptive immune system (30), which both determine the course of Candida infection in hosts (31).…”

Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture

“…The functions of antimicrobial factors in host defense are multi-faceted and range from direct killing of invading microbes (bacteria, fungi, and viruses) to linking innate and acquired immunity. 9,10 We and others have previously shown that epithelial cells in the FRT secrete factors that exhibit potent antimicrobial activity and include human α-defensin-5 (HD5), β-defensins 1-4 (HBD1-4), and secretory leukocyte protease inhibitor (SLPI). [11][12][13] These antimicrobial polypeptides, some of which are induced in response to PAMP exposure, are effective at inhibiting Gram-positive and Gram-negative bacteria, fungi, and enveloped viruses, including Neisseria gonorrhoeae, Chlamydia trachomatis, Candida albicans, Herpes Simplex Virus-2, and Human Immunodeficiency Virus-1.…”